{Reference Type}: Journal Article
{Title}: ArreSTick motif controls β-arrestin-binding stability and extends phosphorylation-dependent β-arrestin interactions to non-receptor proteins.
{Author}: Tóth AD;Soltész-Katona E;Kis K;Guti V;Gilzer S;Prokop S;Boros R;Misák Á;Balla A;Várnai P;Turiák L;Ács A;Drahos L;Inoue A;Hunyady L;Turu G;
{Journal}: Cell Rep
{Volume}: 43
{Issue}: 5
{Year}: 2024 May 28
暂无{DOI}: 10.1016/j.celrep.2024.114241
{Abstract}: The binding and function of β-arrestins are regulated by specific phosphorylation motifs present in G protein-coupled receptors (GPCRs). However, the exact arrangement of phosphorylated amino acids responsible for establishing a stable interaction remains unclear. We employ a 1D sequence convolution model trained on GPCRs with established β-arrestin-binding properties. With this approach, amino acid motifs characteristic of GPCRs that form stable interactions with β-arrestins can be identified, a pattern that we name "arreSTick." Intriguingly, the arreSTick pattern is also present in numerous non-receptor proteins. Using proximity biotinylation assay and mass spectrometry analysis, we demonstrate that the arreSTick motif controls the interaction between many non-receptor proteins and β-arrestin2. The HIV-1 Tat-specific factor 1 (HTSF1 or HTATSF1), a nuclear transcription factor, contains the arreSTick pattern, and its subcellular localization is influenced by β-arrestin2. Our findings unveil a broader role for β-arrestins in phosphorylation-dependent interactions, extending beyond GPCRs to encompass non-receptor proteins as well.